Hispanic adolescents in the U.S. experience significant health disparities, particularly as it relates to drug use, unsafe sexual behaviors and sexually transmitted infections (STIs). In spite of these disparities, a paucity of effective preventive interventions exist for Hispanic adolescents, and even fewer have been disseminated widely (IOM/NRC, 2009). Given that primary care settings are increasingly becoming the entry-point through which parents bring youth with behavioral health concerns, adolescent primary care settings represent ideal, yet underutilized, settings in which to disseminate evidence-based preventive interventions. Preventive interventions which target risk and protective factors within the family, the most proximal and fundamental social system influencing human behavior, have been found to be among the most efficacious interventions in preventing and reducing drug use and sexual risk behaviors. Familias Unidas is a Hispanic-specific, family-based intervention found to be efficacious and effective in preventing and reducing drug use, sexual risk behaviors, and self-reported STIs. Familias Unidas has been cited by the Institute of Medicine report on Preventing, Emotional, and Behavioral among Young People as ready for broad dissemination (IOM/NRC, 2009). To date, however, Familias Unidas has been only tested for efficacy and effectiveness in schools and has not been evaluated for efficacy/effectiveness in primary care. We have adapted and evaluated Familias Unidas for online delivery; successfully retaining 80% of Hispanic parents and their youth (recruited from schools) in the online, eHealth adaptation of Familias Unidas. We have also demonstrated the feasibility and acceptability of delivering eHealth Familas Unidas in primary care. Evaluating innovative eHealth family-based interventions for Hispanic youth whose feasibility and acceptability is established in primary care settings is timely and of high public health significance. Therefore, the proposed study's overarching aim is to evaluate the relative effectiveness and cost effectiveness of eHealth Familias Unidas, compared to a referral to the National Institute Drug Abuse?s (NIDA) online information page for parents of Hispanic youth (referred hereafter as NIDA Online Information). To test the effectiveness of eHealth Familias Unidas Primary Care in preventing drug use, unprotected sexual behavior, and STIs in a universal sample of Hispanic youth, this study will randomize 456 Hispanic youth and their parents to eHealth Familias Unidas or to NIDA Online Information. Participants will be assessed at baseline, 6, 12, 24, and 36 months post baseline. Study hypotheses are that: 1) eHealth Familias Unidas will be effective, relative to NIDA Online Information, in preventing/reducing drug use, unprotected sexual behavior, and STI incidence in Hispanic adolescents over time and 2) Intervention effects will be partially mediated by family functioning for drug use and unprotected sexual behavior and by family functioning and unprotected sexual behavior for STI incidence. The cost effectiveness of eHealth Familias Unidas over a three year follow up will also be estimated.